Temporary pretreatment with the angiotensin II type 1 receptor blocker, valsartan, prevents ischemic brain damage through an increase in capillary density

被引:42
作者
Li, Jian-Mei [1 ]
Mogi, Masaki [1 ]
Iwanami, Jun [1 ]
Min, Li-Juan [1 ]
Tsukuda, Kana [1 ]
Sakata, Akiko [1 ]
Fujita, Teppei [1 ]
Iwai, Masaru [1 ]
Horiuchi, Masatsugu [1 ]
机构
[1] Ehime Univ, Grad Sch Med, Dept Mol Cardiovac Biol & Pharmacol, Tohon, Ehime 7910295, Japan
关键词
angiotensin II type 1 receptor blocker; capillary density; cerebral blood flow; oxidative stress; stroke;
D O I
10.1161/STROKEAHA.107.503458
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose - We investigated the effect of temporary treatment with a nonhypotensive dose of valsartan on ischemic brain damage in C57BL/6 mice. Methods - We separated the mice into 3 groups of valsartan treatment before middle cerebral artery (MCA) occlusion: (1) for 4 weeks: Val (2W, 2W); (2) for 2 weeks followed by its cessation for 2 weeks: Val (2W, -); and (3) no treatment for 4 weeks: Val (-, -). Results - Ischemic volume, DNA damage, superoxide production, and mRNA levels of monocyte chemoattractant protein-1 and tumor necrosis factor-alpha on the ipsilateral side after 24 hours of MCA occlusion were significantly reduced in both Val (2W, 2W) and Val (2W, -) mice compared with those in Val (-, -) mice, whereas these parameters were larger in Val (2W, -) mice than in Val (2W, 2W) mice. Moreover, mice in both the Val (2W, 2W) and Val (2W, -) groups exhibited an increase in cerebral blood flow in the peripheral territory of the MCA 1 hour after MCA occlusion, with increases in endothelial nitric oxide synthase activation and nitric oxide production. Before MCA occlusion, treatment with valsartan did not influence superoxide production or mRNA levels of monocyte chemoattractant protein-1 and tumor necrosis factor-alpha in the brain. However, the capillary density in the brain in both Val (2W, 2W) and Val (2W, -) mice was increased before MCA occlusion. Conclusions - Our results suggest that temporary valsartan treatment could protect against ischemic brain damage even after its cessation, at least in part due to an increase in capillary density.
引用
收藏
页码:2029 / 2036
页数:8
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